The Breast Cancer SPORE will greatly strengthen and expand the breast cancer research of the UAB Comprehensive Cancer Center with an emphasis on translational research. It's themes of Chemoprevention, Gene Therapy, Targeted Immunotherapy, Anti-angiogenesis, Genetic Mechanisms of Oncogenesis, and Mechanisms of Tamoxifen Resistance are all national priority areas. Six research projects involve interdisciplinary investigative teams including: 1) "Preclinical/Clinical Development of Novel Retinoids" provides medicinal chemistry, preclinical toxicology/efficacy and early clinical study of UAB designed reagents; 2) "Hormonal Resistance: Mechanisms and Reversal" explores the mechanisms which induce Tamoxifen resistance and the role of anti- angiogenesis agents in reversal of this process; 3) "Biology and Intermediate Marker Role of a Novel Breast Cancer Oncogene, GKLF" will explore the oncogenic mechanisms resulting from GKLF over- expression and its potential as an intermediate marker in chemoprevention trials; 4) "Gene Therapy Specifically Directed at Tumor Vasculature" will develop novel adenoviral vectors targeted to breast cancer vasculature as mediators of anti-angiogenesis strategies; 5) Polynucleotide Vaccine Therapy of Breast Cancer" will design methods to enhance tumor antigen DNA vaccine induction of anti-tumor immunity in animal models and patients; and 6) "Pre-targeting Radioimmunotherapy of Metastatic Breast Cancer" which will utilize a novel fusion protein composed of single chain antibodies and streptavidin to localize Biotin-DOTA-radioactive isotopes to tumor sites. in animal models and patients. These projects will be supported by three Cores: 1) Administrative/Biostatistics; 2) Tissue Resource and Immunopathology; and 3) Clinical Trials. In addition, the SPORE will have a Career Development Program directed at careers in Breast Cancer Translational Research (5 awards) and a Developmental Research Program (5-6 pilot projects annually). The SPORE has strong institutional commitments and enthusiastic plans for interaction with other SPOREs including our own Ovarian Cancer SPORE. This SPORE will increase scientific discoveries and rapidly translate fundings into innovative clinical trials.